The chief goal is to understand how the hormone vasopressin regulates water excretion by the kidney. Vasopressin's action is mediated through regulation of the molecular water channel aquaporin-2. Based on our studies a decade ago, it is now clear that vasopressin regulates aquaporin-2 in a time frame of seconds to minutes by altering the distribution of the water channel aquaporin-2 between the plasma membrane and the cytoplasm via vesicular trafficking. Trafficking of aquaporin-2 to the plasma membrane renders the cells permeable to water. We are presently using a systems approach to address the mechanisms involved. For this approach, we are integrating protein mass spectrometry, DNA microarrays, mathematical modeling and physiological methods. The following is a summary of work over the past year appearing in the 20 references published from October, 2007 until July, 2008. [unreadable] [unreadable] The first 6 references in the reference list below show publications that have used protein mass spectrometry (1-6) to investigate protein networks involved in regulation of renal water and solute transport, as well as the mass spectrometry tools developed for these studies. The next three references (7-9) deal with studies of vasopressin action using conventional physiological technques. The next three (10-12) are clinically-oriented papers which describe bioengineering work to exploit our recent discovery that normal kidneys excrete exosomes in the urine. Exosomes are are small membrane particles secreted by every cell type facing the urinary space in the kidney. The goal of these studies is to develop the methods infrastructure to allow clinical investigators to isolate urinary exosomes for disease biomarker studies (10-12). The next 5 references describe work focusing on the use of animal models of disease processes to discover the pathophysiological basis of salt and water imbalance disorders (13-17). The 18th paper describes transcriptomics of the renal collecting duct using Affymetrix arrays. The final paper is a review addressing how transgenic and knockout mice have been used to study transport regulation in the kidney.